This study will determine the mechanisms of acquired immunity to experimental leishmaniasis. Established models of local cutaneous, diffusecutaneous, and mucocutaneous leishmaniasis in guinea pigs caused by Leishmania enriettii will be employed. The kinetics and characteristics of the immunological response to infection will be compared in these 3 models. This will involve determining the ability of defined lymphoid cell populations, or serum components taken from animals at various stages of infection and immunity to adoptively immunize normal syngeneic recipients against a standard challenge with viable Leishmania. Experiments will be performed to determine whether the disseminating disease is due to a failure on the part of the host to develop immunity or, alternatively, to an inability to express it. A comparative analysis of the host response in these different forms of infection will include exeriments designed to meassre the acquisition and relevance of macrophage activation, particularly as it may relate to promotion of the disease by ensuring the rapid intramacrophage location of the parasite. The hypothesis will be tested that the presence of a persistent local infection in an otherwise systemically immune host is caused by the presence of parasite-dependent mechanisms that suppress the expression of immunity at the site of infection. By measuring the quantity and quality of the immune response and the capacity to express this immunity in models of experimental leishmaniasis which closely resemble the clinical spectrum of the disease in man, it is anticipated that a better understanding of the reasons for the chronicity and metastasis of human infection will result.